Insecticide resistance is a serious obstacle to the effective control of insect vectors of disease. My research program is directed toward understanding the genetic and population processes influencing the evolution of insecticide resistance in vector populations. The long-term goal of my work is to provide the information necessary to design vector control strategies which minimize the rate of evolution of resistance. In the mosquito Culex quinquefasciatus, resistance to organophosphate insecticides is associated with a highly active esterase allozyme, designated EST-B1. The molecular basis of high esterase activity in resistant individuals is amplification (increase in copy number) of the EST-B1 gene. To understand the dynamics of amplified EST-B1 genes in populations we need information about how genetic processes interact with insecticidal selection to produce individuals with high esterase activity, the stability properties of these high activity phenotypes, and how esterase activity phenotype affects reproductive fitness in the presence of absence of insecticide. The specific objectives of the proposed research are: 1) A chromosome carrying and EST-B1 gene amplification which results in a small bud readily detectable increase in esterase activity over susceptible strain levels will be isolated from the S-Y strain of C quinquefasciatus which exhibits a wide range of esterase activity phenotypes. Strains carrying this chromosome will be subjected to insecticidal selection to assess changes in the frequency and distribution of esterase activity phenotypes over time. This experiment will provide a rough estimate of the frequency with which esterase activity variants arise, and how quickly high esterase activity phenotypes are produced by selection. 2) The stability of high esterase activity phenotypes produced by selection will be determined by examining changes in the frequency and distribution of esterase activity phenotypes over time in strains released from insecticidal selection. 3) The relationship between esterase activity phenotype and the ability to survive insecticide treatment will be determined in the variable S-Y strain by subjecting samples of Individuals to different concentrations of insecticide and measuring the esterase activity of survivors. 4) The relationship between esterase activity phenotype and reproductive fitness will be determined in the variable S-Y strain by measuring esterase activity and several components of reproductive fitness of individuals.